Kobayashi T
Jpn J Antibiot. 1983 Feb;36(2):464-76.
Clostridium difficile has been implicated as the major cause of antimicrobial associated colitis or diarrhea. C. difficile was found in stools from 21 of 120 healthy subjects. C. difficile was found in stools from 8 of 9 patients with antimicrobial associated pseudomembranous colitis and in stools from 16 of 96 patients with antimicrobial associated diarrhea. The cytopathic toxin to HeLa cell neutralized by antitoxin to C. difficile was found in stools from all patients with antimicrobial associated colitis or diarrhea. Of 21 strains isolated in the stools from healthy subjects, 19 strains were toxigenic. Some of them were highly toxigenic strains. Such highly toxigenic strains, however, did not give rise to any clinical symptoms probably because of the limited number of this organisms in the normal flora of human intestines; the number of C. difficile ranged between less than 10 and 10(2) level per gram of stool when the organism was found. Of the 24 isolates from antimicrobial associated colitis or diarrheal patients, 4 were highly toxigenic. The susceptibilities of 65 isolates to various antimicrobial agents were determined by the agar dilution technique. All of the 65 strains were inhibited by low concentration of rifampicin, metronidazole, vancomycin, ampicillin and amoxicillin. The isolates were highly resistant to gentamicin, cefoxitin, cefotaxime and cefmenoxime. Wide variations in susceptibility of C. difficile strains to erythromycin, clindamycin and lincomycin were found. The studies have shown that subinhibitory concentrations of clindamycin, cephalothin and amoxicillin cause an increase in cytotoxin levels of C. difficile during broth culture. The increase in supernatant toxin levels occurs concomitant with a decrease in sonicated cell extract toxin levels. The data suggest that a number of factor can cause a release of toxin from C. difficile into the surrounding medium or the intestine.
艰难梭菌被认为是抗菌药物相关性结肠炎或腹泻的主要病因。在120名健康受试者的粪便中，有21人的粪便中发现了艰难梭菌。在9例抗菌药物相关性假膜性结肠炎患者的粪便中，有8人的粪便中发现了艰难梭菌；在96例抗菌药物相关性腹泻患者的粪便中，有16人的粪便中发现了艰难梭菌。在所有抗菌药物相关性结肠炎或腹泻患者的粪便中，均发现了能被艰难梭菌抗毒素中和的对HeLa细胞具有细胞病变作用的毒素。在健康受试者粪便中分离出的21株菌株中，有19株产毒。其中一些是高毒力菌株。然而，这些高毒力菌株可能未引起任何临床症状，这可能是因为人体肠道正常菌群中该菌数量有限；当发现该菌时，每克粪便中艰难梭菌的数量在少于10至10²水平之间。在从抗菌药物相关性结肠炎或腹泻患者中分离出的24株菌株中，有4株是高毒力菌株。采用琼脂稀释法测定了65株分离株对各种抗菌药物的敏感性。所有65株菌株均被低浓度利福平、甲硝唑、万古霉素、氨苄西林和阿莫西林抑制。这些分离株对庆大霉素、头孢西丁、头孢噻肟和头孢甲肟高度耐药。发现艰难梭菌菌株对红霉素、克林霉素和林可霉素的敏感性差异很大。研究表明，在肉汤培养过程中，亚抑菌浓度的克林霉素、头孢噻吩和阿莫西林会导致艰难梭菌细胞毒素水平升高。上清液毒素水平的升高与超声破碎细胞提取物毒素水平的降低同时发生。数据表明，多种因素可导致艰难梭菌将毒素释放到周围培养基或肠道中。
